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An open-label, active-controlled study of NPC-25 in patients with hypozincemia (noninferiority study) (NPC-25-3)

A noninferiority study of NPC-25 in patients with hypozincemia

216

The gender of subjects who received the study drug in the Full Analysis Set (FAS) was 43.7% (45/103) and 37.4% (40/107) male and 56.3% (58/103) and 62.6% (67/107) female in the NPC-25 group and in the NOBELZIN group, respectively. The median (range) age was 72.0 (10, 93) and 64.0 (13, 86) in the NPC-25 group and in the NOBELZIN group, respectively. The median (range) serum zinc concentration at the start of treatment were 62.0 (40, 69) micro g/dL and 61.0 (37, 70) micro g/dL in the NPC-25 group and in the NOBELZIN group, respectively.

216 participants were enrolled and randomly assigned 1: 1 to the NPC-25 group (n=107) or the NOBELZIN group (n=109). All randomized subjects received at least 1 dose of investigational medicinal product. The FAS comprised 210 participants (n=103, NPC-25; n=107, NOBELZIN), excluding 4 individuals in the NPC-25 group and 2 in the NOBELZIN group with an investigational drug administration duration of <=20 days. The number of completed administrations during the Efficacy Evaluation Period was 193 (n=95, NPC-25; n=98, NOBELZIN), and there were 23 cases of discontinuation (n=12, NPC-25; n=11, NOBELZIN). Participants in the NPC-25 group requiring continued administration were permitted to continue treatment for up to a maximum of 52 weeks. Of the 59 cases that transitioned to continued administration, 54 completed the continued administration, and 28 cases completed administration up to 52 weeks.

Time Frame Treatment period: Efficacy Evaluation Period was defined as the period from the start of administration to (a) time of achievement of Primary Endpoint (the maintenance of the target serum zinc concentration range for 8 weeks at the same dose) or (b) by Week 24 in patients who did not achieve Primary Endpoint. However, for patients who need to continue the treatment in the NPC-25 group, treatment can be continued for up to 52 weeks. Thus, Safety in this study was evaluated for both the entire period in the NPC-25 group and the Efficacy Evaluation Period in the NPC-25 group and in the NOBELZIN group. Entire Period: The incidence of adverse events in the NPC-25 group was 75.7% (81/107 patients). The incidence of serious adverse events in the NPC-25 group was 9.3% (10/107 patients). In the NPC-25 group, adverse events that were observed in more than 2% of cases were, Pyrexia (8.4%: 9/107), COVID-19 and Nasopharyngitis (7.5%: 8/107 for each), Blood copper decreased and Dizziness (4.7%: 5/107 for each), Anaemia, Constipation, Nausea, Ligament sprain, Amylase increased, Lipase increased, Back pain, Headache, and Pruritus (3.7%: 4/107 for each), Abdominal discomfort, Diarrhoea, Oedema peripheral, Hepatic function abnormal, Tinea pedis, Arthropod sting, Arthralgia, Eczema (2.8%: 3/107 for each). Efficacy Evaluation Period: The incidence of adverse events in the NPC-25 group and in the NOBELZIN group were 61.7% (66/107 patients) and 57.8% (63/109 patients), respectively. The incidence of serious adverse events in the NPC-25 group and in the NOBELZIN group were 4.7% (5/107 patients) and 8.3% (9/109 patients), respectively. In the NPC-25 group, adverse events that were observed in more than 2% of cases were, Pyrexia (5.6%: 6/107), Blood copper decreased (4.7%: 5/107), Anaemia, and Nausea (3.7%: 4/107 for each), Abdominal discomfort, Diarrhoea, Hepatic function abnormal, Back pain, Dizziness, and Headache (2.8%: 3/107 for each). In the NOBELZIN group, adverse events that were observed in more than 2% of cases were, Nausea(6.4%: 7/109), COVID-19 (4.6%: 5/109), Vomiting, Nasopharyngitis, and Blood copper decreased(3.7%: 4/109 for each), Abdominal discomfort, Diarrhoea, Stomatitis, Sinusitis, and Amylase increased(2.8%: 3/109 for each).

The "Proportion of participants in whom the target serum zinc concentration was maintained for 8 weeks at the same dose by 24 weeks after the start of administration," the primary endpoint, was 86.4% (89/103 patients) in the NPC-25 group and 80.4% (86/107 patients) in the NOBELZIN group. The difference in the proportion between the NPC-25 group and the NOBELZIN group was 6.0% (95% confidence interval [CI]: -4.2% to 16.3%), and the non-inferiority of the NPC-25 group to the NOBELZIN group was demonstrated since the lower limit of the 95% confidence interval exceeded the non-inferiority margin of -15%. For the secondary endpoint, "Changes in the proportion of participants in whom the target serum zinc concentration was maintained for 8 weeks at the same dose over time," a tendency toward earlier achievement of the primary endpoint was seen in the NPC-25 group compared to the NOBELZIN group. In addition, for the "Proportion of participants in whom the target serum zinc concentration could be maintained for 8 weeks by dose level," a tendency toward achievement of the primary endpoint was seen at lower doses in the NPC-25 group than in the NOBELZIN group. For other secondary endpoints, many parameters were numerically the same or higher in the NPC-25 group than in the NOBELZIN group. Moreover, a stable effect for the most part was maintained during long-term administration.

Non-inferiority of NPC-25 to NOBELZIN was confirmed in terms of efficacy. Moreover, a stable effect for the most part was maintained during long-term administration. The most common adverse drug reactions in the NPC-25 group were those predicted from reports on zinc preparations given to date and there were no major issues in the comparison to the NOBELZIN group.

Nov. 21, 2024

https://www.sciencedirect.com/science/article/pii/S0946672X24001780?via%3Dihub

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071210102

Kitamura Motohiro

Nobelpharma Co., Ltd.

NMF Kayabacho Bldg., 1-17-24, Shinkawa, Chuo-ku, Tokyo

kitamura@nobelpharma.co.jp

Kitamura Motohiro

Nobelpharma Co., Ltd.

NMF Kayabacho Bldg., 1-17-24, Shinkawa, Chuo-ku, Tokyo

+81-3-6670-3800

kitamura@nobelpharma.co.jp

Complete

Jan. 06, 2022

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

Patients who have provided written informed consent and are confirmed to meet the following criteria (1) and (2) at the time of enrollment.
(1) Patients whose serum zinc concentrations (measured at institutions) both at the time of enrollment and within 8 weeks before the start of treatment are less than 70 micro g/dL
(2) Patients weighing at least 30 kg who are capable of taking tablets orally at the time of providing informed consent, regardless of sex and inpatient or outpatient status

Patients falling under any of the following criteria at the time of enrollment will be excluded.
(1) Patients with fulminant hepatitis
(2) Patients with malignant tumors
(3) Patients with serious heart, blood, kidney or pancreatic disease, or the like
(4) Patients with serum albumin levels of less than 2.8 g/dL
(5) Patients with serum copper concentrations below the lower limit of the reference range
(6) Patients who have allergies or hypersensitivity to zinc-containing preparations (including supplements)
(7) Patients who have taken zinc-containing preparations or zinc-containing supplements that are prohibited from being used concomitantly within 12 weeks before enrollment.
(8) Patients who are or may possibly be pregnant, or wish to become pregnant during the study period
(9) Patients who participated in other clinical trials within 12 weeks before enrollment.
(10) Patients whose participation in the study is considered inappropriate by the investigator (subinvestigator).

Both

hypozincemia

NPC-25 group:Take the drug orally once daily after a meal.
NOBELZIN group:Take the drug orally once to three times daily after meals.

The proportion of subjects who become able to maintain the target serum zinc concentration range (80 to <200 micro g/dL) for 8 weeks at the same dose, within 24 weeks of the start of the treatment.

(1) Time from the start of treatment to first reaching the target serum zinc concentration range (80 to <200 micro g/dL)
(2) Time from the start of treatment to first reaching the maintenance of the target serum zinc concentration range (80 to <200 micro g/dL) for 8 weeks at the same dose
(3) Changes over time in serum zinc concentrations

+81-92-682-7000

Dec. 06, 2021

none